Electrospinning had recently gained interest as a method of scaffold fabrication in tissue engineering (Pham, Q. P., Sharma, U. et al., 2006, Tissue Engineering, vol. 12, p. 1197-1211). In this process, long and fine threads are drawn from droplets of polymer by the application of a high voltage electric field (Li, D. & Xia, Y. N., 2004, Advanced Materials, vol. 16, p. 1151-1170). The result is a highly porous mesh of nanofibers that resemble the connective tissue in an extracellular matrix (Han, D. & Guoma, P. I.; 2006; Nanomedicine: Nanotechnology, Biology and Medicine; vol. 2, p. 37-41). This biomimicry has been shown to positively influence cell-scaffold interaction such as cell attachment, migration, proliferation and function (Lindberg, K. & Badylak, S. F., 2001, Burns, vo. 27, p. 254-266; Schindler, M. et al., 2005, Biomaterials, vol. 26, p. 5624-5631; Smith, L. A. & Ma, P. X., 2004, Colloids and Surfaces B-Biointerfaces, vol. 39, p. 125-131).
However, the major obstacle with the use of electrospun scaffolds is the lack of control of its pore size, which is inherently small (typically less than 5 μm). This is due to nature of the electrospinning process that randomly deposits layers of non-woven fibers on each other. Few researchers have addressed this issue, but it has several implications. Firstly, cell infiltration is poor as cells are unable to permeate through the small pores (Stankus, J. J., Guan, J. J., et al., 2006, Biomaterials, vol. 27, p. 735-744). Cell-scaffold interaction is thus limited to the surface whereas an ideal tissue engineered construct has to be three-dimensional. Secondly, the small pores prevent vascular ingrowth (Brauker, J. H. et al., 1995, Journal of Biomedical Materials Research, vol. 29, p. 1517-1524). This limits the thickness of the scaffold, as cells within the construct rely on diffusion from the vasculature for nutrient and waste transfer (Jain, R. K., Au, P., et al., 2005, Nature Biotechnology, vol. 23, p. 821-823; Levenberg, S. et al., 2005, Nature Biotechnology, vol. 23, p. 879-884). Thirdly, the lack of control of the pore size prevents one from optimizing the electrospun scaffold for its intended tissue application (Smith, L. A. & Ma, P. X., 2004, supra). This is because specific cell types interact optimally with the scaffold when it is of a certain pore size (Marshall, A. J. et al., 2004, Abstracts of Papers of the American Chemical Society, vol. 228, p. U386-U386). These factors limit the versatility of electrospun scaffolds in tissue engineering.
There have been two strategies used to improve cell infiltration into electrospun scaffolds. One is the use of filtration seeding bioreactors but these are complicated and result in an uneven cell distribution (Li, Y., Ma, T., Kniss, et al., 2001, Biotechnology Progress, vol. 17, p. 935-944). Stankus, J. J., Guan, J. J., et al. (2006, supra) adopted a different approach by simultaneously electro spraying cells in situ while electrospinning a polymeric mesh. With this microintegration technique, the group was able to obtain high cell densities within a thick construct, which could be maintained with a perfusion bioreactor. While these techniques improve cell density, they do not address the lack of vascularization when these constructs are implanted, as their pore size remains small.
Thus a need remains for the manufacture of electrospun scaffolds which meet the requirements for tissue engineering.